Parkinsonian Symptoms Research Articles

Assessment of Sexual Dysfunction in Male Patients with Young-Onset Parkinson’s Disease: A Case-Control Study

Introduction: There is a need for a comprehensive assessment of sexual dysfunction in patients with young-onset Parkinson’s disease (PD) to better understand its impact on this population. This study aimed to assess sexual dysfunction in patients with young-onset PD. Methods: This case-control study was conducted using a self-administered International Index of Erectile Function Scale (IIEF) questionnaire. The questionnaire included questions related to sexual function, including the ability to achieve and maintain erection and sexual desire. The participants included 30 individuals with young-onset PD and 30 controls without PD who were matched for age and gender. Results: The study enrolled 30 patients with an average age of 37.2 ± 5.29 years and PD symptom duration ranging from less than two years to over two years. Most patients were classified as having stage 2 or 3 PD and exhibited a range of symptoms, such as bradykinesia, tremors, rigidity, and postural instability. The findings revealed that 40% of the PD group experienced moderate erectile dysfunction, while 23.33% reported severe dysfunction, in contrast to the absence of dysfunction observed in the control group. The analysis indicated that patients with a disease duration of less than two years had higher scores across all five components of the IIEF questionnaire. Furthermore, anxiety, depression, increased medication use, and disease severity significantly affected sexual function. Conclusion: This study highlights the impact of young-onset PD on sexual function and underscores the importance of the early recognition and management of sexual dysfunction in patients with PD.

C9orf72 Gene-Associated Frontotemporal Dementia Mimicking Autoimmune Pathology.

The C9orf72 mutation can manifest in diverse clinical ways, including rapid cognitive decline, parkinsonism, or late-life neuropsychiatric symptoms, sometimes mimicking autoimmune encephalitis. A 64-year-old female presented to the autoimmune neurology clinic with rapidly progressive dementia (RPD) associated with episodes of headache, confusion, auditory hallucinations, and abnormal electroencephalogram. She was treated empirically at an outside hospital for possible autoimmune encephalitis with intravenous methylprednisolone, but there was no improvement, and rapid cognitive decline continued. Family history was notable for RPD with akinetic mutism in her sister, sudden severe depression followed by parkinsonism with progressive dementia in her father in his 60s, and late-life gradually progressive dementia in her mother. Additional testing revealed a low titer positive contactin-associated protein-like 2 (CASPR2) immunoglobulin G (IgG) in the serum and elevated CSF 14-3-3 protein. CSF CASPR2 IgG and real-time quaking-induced conversion for Creutzfeldt-Jakob disease were negative. Brain MRI showed normal parenchymal volume. Genetic testing was conducted, which identified a heterozygous pathogenic hexanucleotide tandem repeat expansion in the C9orf72 gene. This case underscores the phenotypic variability of C9orf72 mutation and the importance of a detailed family history exploring young or atypical deaths and neuropsychiatric symptoms or behavioral changes. Genetic etiologies are crucial to consider in those with a family history concerning autosomal dominant inheritance patterns of early-onset dementia, parkinsonism, or late-onset psychiatric disease. Emphasis is placed on considering alternative etiologies early, particularly when there is no response to first-line immunomodulation for suspected autoimmune dementia.

Neuronal threshold functions: Determining symptom onset in neurological disorders

Synaptic networks determine brain function. Highly complex interconnected brain synaptic networks provide output even under fluctuating or pathological conditions. Relevant to the treatment of brain disorders, understanding the limitations of such functional networks becomes paramount. Here we use the example of Parkinson’s Disease (PD) as a system disorder, with PD symptomatology emerging only when the functional reserves of neurons, and their interconnected networks, are unable to facilitate effective compensatory mechanisms. We have denoted this the “threshold theory” to account for how PD symptoms develop in sequence. In this perspective, threshold functions are delineated in a quantitative, synaptic, and cellular network context. This provides a framework to discuss the development of specific symptoms. PD includes dysfunction and degeneration in many organ systems and both peripheral and central nervous system involvement. The threshold theory accounts for and explains the reasons why parallel gradually emerging pathologies in brain and peripheral systems generate specific symptoms only when functional thresholds are crossed, like tipping points. New and mounting evidence demonstrate that PD and related neurodegenerative diseases are multisystem disorders, which transcends the traditional brain-centric paradigm. We believe that representation of threshold functions will be helpful to develop new medicines and interventions that are specific for both pre- and post-symptomatic periods of neurodegenerative disorders.

Modeling the pre-symptomatic stage of hemi-parkinsonian state in animals (rodents and monkeys)

The behavioral and functional states preceding the onset specific parkinsonian symptoms were studied at an early (pre-symptomatic) stage of hemi-parkinsonian syndrome development in rodents and monkeys. The pre-symptomatic stage of the hemi-parkinsonian syndrome was determined in rodents (mice and rats) treated by chronic administration of low doses of rotenone toxin. The consecutive steps of neuropathological traits development in rodents included the cognitive impairment at the 1st-2nd week of exposure to rotenone, minor movement disorders at the 3st-4nd week before the onset of severe motor dysfunction as well as some biochemical indicators. The latencies and amplitudes of visually guided saccades (VGS) while conditioned instrumental task performing were studied in nonhuman primates (Macaca mulatta) chronically treated with low doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The elongation of VGS latencies and the decline of their accuracy were revealed with development of MPTP-induces syndrome but conditioned instrumental performance was not affected. The negative behavioral effects manifested in animals at the pre-symptomatic stage of toxins induced disease both in the rotenone model in rodents and in MPTP model in monkeys suggesting them as early markers of a hemi-parkinsonian syndrome.

Self-Adjusting Deep Brain Stimulation Cuts Parkinson's Symptoms 50 Percent More Than Conventional Method

Self-Adjusting Deep Brain Stimulation Cuts Parkinson's Symptoms 50 Percent More Than Conventional Method

SEND-PD in Parkinsonian Syndromes: Results of a Monocentric Cross-Sectional Study.

Neuropsychiatric symptoms in particular impair health-related quality of life (QoL) of patients with Parkinson's disease and atypical Parkinsonian syndromes. For this reason, various scales have been developed for detection of neuropsychiatric symptoms, such as the Scale for evaluation of neuropsychiatric disorders in Parkinson's disease (SEND-PD). First, the objective of this study was to explore the interrelation between the SEND-PD and clinical parameters in patients with Parkinson's disease and thus confirm its validity. In addition, the applicability in a well-defined cohort of patients with atypical Parkinsonian syndromes was investigated for the very first time. A clinically well-defined cohort of 122 patients with Parkinson's disease (PD), 55 patients with Progressive Supranuclear Palsy (PSP) and 33 patients with Multiple System Atrophy (MSA) were analyzed. First, the SEND-PD was correlated with established disease-specific scores in patients with PD. Next, the results of the SEND-PD were compared between the different Parkinsonian syndromes. The SEND-PD showed a strong significant correlation with several scores, especially the UPDRS I (Rho = 0.655) and GDS-15 (Rho = 0.645). Depressive burden was significantly higher in MSA patients in comparison to the PD patient cohort (PD, 3.8 ± 3.3; MSA, 5.45 ± 3.87), while PSP patients showed significantly less psychotic (PD 1.6 ± 2.1; PSP 0.6 ± 0.9) and impulse control disorders (PD 0.3 ± 1.0; PSP 0.02 ± 0.1). The SEND-PD is a useful, brief and highly applicable screening tool for neuropsychiatric symptoms in PD, but not in atypical Parkinsonism, as their unique neuropsychiatric symptom composition is not fully captured.

Shisandra Decoction Alleviates Parkinson's Disease Symptoms in a Mouse Model Through PI3K/AKT/mTOR Signalling Pathway.

The present study aimed to characterize neuroprotective effects of Schisandra Decoction (Sch D) treatment in a mouse model of Parkinson's disease (PD), and to explore underlying mechanisms focused on the mammalian target of rapamycin (mTOR) signaling pathway. 50 male C57 BL/6 mice were randomly assigned to either control (n = 10) or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model (n = 40) groups. PD mice were further divided into four groups of ten mice each: MPTP group, LY294002 group, Sch D group, and LY2940002 + Sch D group. Mice from each group were assessed in pole climbing, rotary rod and open field tests. Brain Tyrosine hydroxylase (TH) protein was observed using immunohistochemistry. mRNA levels of PTEN, PI3K and LC3 in brain tissue were measured using RT-PCR. Protein levels of PTEN, PI3K, Akt, p-Akt, mTOR, p-mTOR, p70s6K, p62, LC3II / I, α-synuclein (α-syn), TH in brain tissue were assessed by Western blotting (WB). In behavioral tests, PD mice treated with Sch D showed reduced pole climbing time, longer rotarod duration, and greater distance traveled. In terms of neuroprotection, PD mice in the Sch D group exhibited higher levels of TH protein and enhanced α-syn clearance. Regarding autophagy, compared to the control group, mice in the MPTP group had elevated PTEN protein expression, which inhibited PI3K, p-AKT/AKT, and p-mTOR/mTOR protein levels, decreased LC3II/I protein expression, and increased P62 protein expression. Treatment with Sch D reversed these effects. Sch D reduces α-syn aggregation in the brains of MPTP-induced PD model mice, exerts neuroprotective effects, and improves motor function. Additionally, Sch D inhibits autophagy through the PI3K/AKT/mTOR pathway. The neuroprotective effect of Sch D may involve the suppression of abnormal autophagy and its antioxidant properties, which indirectly reduces α-syn accumulation. Future studies should assess the impact of Sch D on oxidative stress markers to evaluate its antioxidant effects.

Pattern of Nonmotor Symptoms in Patients with Idiopathic Parkinson's Disease in a Tertiary Care Hospital of Rural Eastern India.

Idiopathic Parkinson's disease (IPD) is associated with a spectrum of nonmotor symptoms (NMS) that contribute as much to the burden of the disease as the more obvious motor abnormalities. There is a paucity of literature determining the association between NMS and the severity of IPD, especially in rural eastern parts of India. This study explores the frequency of NMS in patients with IPD and determines the association between NMS and the severity of IPD. A cross-sectional observational study involving 65 serially enrolled IPD patients (diagnosed as per United Kingdom Parkinson's Disease Society Brain Bank Clinical Diagnostic Criteria) was conducted over a period of 18 months. The patients were evaluated for disease severity as per the Hoehn and Yahr scale (original) and were subsequently evaluated with a predesigned and validated Parkinson's Disease Non-Motor Symptoms Questionnaire. Pearson's Chi-squared test for independence of attributes or Fisher's exact test was used for comparison of categorical variables across the groups. Continuous variables were compared using a one-way analysis of variance (ANOVA) test. The most common presenting NMS of IPD was low mood (n = 61; 93.85%), followed by apathy (n = 59; 90.77%), impaired concentration (n = 58; 89.23%), restless leg (n = 54; 83.08%), and tenesmus (n = 54; 83.08%). A majority of the neuropsychiatric symptoms, autonomic dysfunctions, sleep abnormalities, gastrointestinal manifestations, and sensory abnormalities individually showed a statistically significant relation with the severity of IPD. Common presenting NMS include neuropsychiatric manifestations, autonomic symptoms, sleep-related symptoms, and gastrointestinal manifestations. Most of the NMS are significantly related to disease severity.

Chondroitin sulfate modulates oxidative stress and inflammation in the substantia nigra via gut microbiota regulation: Mechanistic insights into Parkinson's disease treatment

Hydrogen sulfide (H2S) is a bioactive gas with potential neuroprotective properties. This study explores the therapeutic efficacy of chondroitin sulfate (CS) in a Parkinson's disease (PD) mouse model by evaluating its impact on behavior, gut microbiota composition, substantia nigra (SN) pathology, oxidative stress, and inflammation. Behavioral tests indicate that CS improves cognitive function and learning abilities in PD mice. Gut microbiota analysis and fecal H2S content measurement reveal that CS fosters the growth of Desulfovibrio and boosts H2S production, respectively. Further examination shows that CS treatment enhances antioxidant defenses, reduces inducible nitric oxide synthase (iNOS)-mediated inflammation, and alleviates PD-related pathology and α-synuclein overexpression in the SN. These findings suggest that CS modulates the gut microbiota and its metabolic product, H2S, potentially improving PD symptoms through the gut-brain axis.

Targeting modulation of intestinal flora through oral route by an antimicrobial nucleic acid-loaded exosome-like nanovesicles to improve Parkinson’s disease

Parkinson’s disease (PD) is one of the most prevalent neurodegenerative diseases. It is usually accompanied by motor and non-motor symptoms that seriously threaten the health and the quality of life. Novel medications are urgently needed because current pharmaceuticals can relieve symptoms but cannot stop disease progression. The microbiota-gut-brain axis (MGBA) is closely associated with the occurrence and development of PD and is an effective therapeutic target. Tetrahedral framework nucleic acids (tFNAs) can modulate the microbiome and immune regulation. However, such nucleic acid nanostructures are very sensitive to acids which hinder this promising approach. Therefore, we prepared exosome-like nanovesicles (Exo@tac) from ginger that are acid resistant and equipped with tFNAs modified by antimicrobial peptides (AMP). We verified that Exo@tac regulates intestinal bacteria associated with the microbial-gut-brain axis in vitro and significantly improves PD symptoms in vivo when administered orally. Microbiota profiling confirmed that Exo@tac normalizes the intestinal flora composition of mouse models of PD. Our findings present a novel strategy for the development of PD drugs and the innovative delivery of nucleic acid nanomedicines.

Convolutional neural network based detection of early stage Parkinson’s disease using the six minute walk test

The heterogeneity of Parkinson’s disease (PD) presents considerable challenges for accurate diagnosis, particularly during early-stage disease, when the symptoms may be extremely subtle. This study aimed to assess the accuracy of a convolutional neural network (CNN) technique based on the 6-min walk test (6MWT) measured using wearable sensors to distinguish patients with early-stage PD (n = 78) from healthy controls (n = 50). The participants wore six sensors, and performed the 6MWT. The time-series data were converted into new images. The results revealed that the gyroscopic vertical component of the lumbar spine displayed the highest classification accuracy of 83.5%, followed by those of the thoracic spine (83.1%) and right thigh (79.5%) segment. These findings suggest that the 6MWT and CNN models may facilitate earlier diagnosis and monitoring of PD symptoms, enabling clinicians to provide timely treatment during the critical transition from normal to pathologic gait patterns.

Symptoms and Psychosocial Factors on Quality of Life and Life Satisfaction in People with Parkinson’s Disease

Abstract Background Parkinson’s disease (PD) is one of the most common neurodegenerative diseases estimated to touch 9.3 million people worldwide by 2030. Motor and non-motor symptoms of PD have a debilitating effect on people with PD’s quality of life (QoL) and life satisfaction (LS). This study aims to explore the factors influencing people with PD’s lives in Ireland. Methods The sample comprised 827 participants, recruited through crowd-sourcing and snowball sampling. Participants were asked to complete a 30-minute survey online or on paper. The survey collected data on motor and non-motor symptoms, social connectedness, self-efficacy, stigma, QoL and LS. A series of linear and multiple regressions assessed the relationships between people with PD’s symptoms, psychosocial factors and their QoL and LS. Results Low self-efficacy and high levels of stigma were predictive of low QoL and LS, while low social connectedness was associated only with low QoL. Results showed reduced dexterity with hand/eye coordination, anxiety, apathy, pain and fatigue contributed to LS, whereas reduced dexterity with hand/eye coordination, shaking/tremors, stiffness of movement, freezing of gait, cognitive problems, hallucinations, apathy, compulsive behaviours, sleeping disorders, pain and urinary incontinence were contributors of QoL. Conclusion This study can provide insights into the factors influencing people with PD’s QoL and LS. Data can promote the development of therapeutic interventions targeting PD non-motor symptoms, which are often dismissed by clinicians. Finally, findings can inform the development of health and social policies and educate the general public to dissolve the stigma associated with PD.

Exercise training upregulates CD55 to suppress complement-mediated synaptic phagocytosis in Parkinson’s disease

The primary pathological change in Parkinson’s disease (PD) is the progressive degeneration of dopaminergic neurons in the substantia nigra. Additionally, excessive microglial activation and synaptic loss are also typical features observed in PD samples. Exercise trainings have been proven to improve PD symptoms, delay the disease progression as well as affect excessive microglial synaptic phagocytosis. In this study, we established a mouse model of PD by injecting mouse-derived α-synuclein preformed fibrils (M-α-syn PFFs) into the substantia nigra, and demonstrated that treadmill exercise inhibits microglial activation and synaptic phagocytosis in striatum. Using RNA-Seq and proteomics, we also found that PD involves excessive activation of the complement pathway which is closely related to over-activation of microglia and abnormal synaptic function. More importantly, exercise training can inhibit complement levels and complement-mediated microglial phagocytosis of synapses. It is probably triggered by CD55, as we observed that CD55 in the striatum significantly increased after exercise training and up-regulation of that molecule rescued motor deficits of PD mice, accompanied with reduced microglial synaptic phagocytosis in the striatum. This research elucidated the interplay among microglia, complement, and synapses, and analyzed the effects of exercise training on these factors. Our work also suggested CD55 as a complement-relevant candidate molecule for developing therapeutic strategies of PD.Graphical

Orchestrating AMPK/mTOR signaling to initiate melittin-induced mitophagy: A neuroprotective strategy against Parkinson's disease

Apitherapy has a long history in treating Parkinson's disease (PD) in humans, with evidence suggesting that bee venom (BV) can mitigate Parkinson's symptoms. Central to BV's effects is melittin (MLT), a principal peptide whose neuroprotective mechanisms in PD are not fully understood. The study investigated the effects of MLT on an experimental PD model in mice and dopaminergic neuron cells, induced by MPTP or MPP+. We concentrate on the autophagic response elicited by MLT during PD pathogenesis. The findings showed that MLT was shown to protect against MPP+/MPTP cytotoxicity and preserve tyrosine hydroxylase (TH) levels, indicating neuronal safeguarding. Remarkably, MLT instigated mitophagy, enhancing mitochondrial homeostasis in MPP+-exposed SH-SY5Y cells. Further, MLT's promotion of mitophagy was confirmed to be AMPK/mTOR signaling-dependent. Validation using Bafilomycin A1, an autophagy inhibitor, confirmed MLT's neuroprotective role, with autophagy inhibition negating MLT's benefits and reducing TH preservation. These findings illuminate MLT's therapeutic potential, particularly its modulation of mitochondrial dysfunction in PD pathology. Our research advances the understanding of MLT's mechanistic action, emphasizing its role in mitochondrial autophagy and AMPK/mTOR signaling, offering a novel perspective beyond the symptomatic relief associated with BV.

TMS and tDCS as potential tools for the treatment of cognitive deficits in Parkinson's disease: a meta-analysis.

Cognitive deficits are common nonmotor symptoms in Parkinson's disease (PD). Non-Invasive Brain Stimulation (NIBS) could be a potential aid to prevent or delay dementia progression in this clinical population. However, previous studies reported controversial results concerning their efficacy on cognitive symptoms of PD. Hence, the present meta-analysis aims to systematically examine the effects of NIBS as possible treatments for PD cognitive impairments. Understanding NIBS' impact on these symptoms may be of outstanding importance to implement new therapeutic strategies and improve the patients' quality of life. EMBASE, Scopus, and PubMed databases were systematically searched for consecutive studies published from 2000 to March 2023 describing Randomized Controlled Trials studies evaluating the effect of NIBS on PD cognitive symptoms. From the included studies, data concerning neuropsychological tests were extracted and grouped into six cognitive domains, separately analyzed. Hedge's method was computed as the effect size measure of the extracted data; heterogeneity among studies and publication bias were also assessed. The Cochrane's RoB2 tool was used to evaluate the risk of bias for each of the included studies. After database searching and screening of texts, sixteen studies met the inclusion criteria. No significant results emerged from any investigated cognitive domain when comparing NIBS and sham treatments. Several factors may have contributed to the lack of effects; among these, methodological choices, the small sample of studies, the high heterogeneity of data and stimulation protocols pose the need for more controlled studies to highlight the potentiality of NIBS as a future treatment for PD cognitive impairments.

Adjustability of Gait Speed in Clinics and Free-Living Environments for People With Parkinson's Disease.

Gait speed is regulated by varying gait parameters depending on the diverse contexts of the environment. People with Parkinson's disease (PwPD) have difficulty adapting to gait control in their environment; however, the relationships between gait speed and spatiotemporal parameters in free-living environments have not been clarified. This study aimed to compare gait parameters according to gait speed in clinics and free-living environments. PwPD were assessed at the clinic and in a free-living environment using an accelerometer on the lower back. By fitting a bimodal Gaussian model to the gait speed distribution, gait speed was divided into lower and higher speeds. We compared the spatiotemporal gait parameters using a 2 × 2 (environment [clinic/free-living] × speed [lower/higher]) repeated-measures analysis of variance. Associations between Parkinson's disease symptoms and gait parameters were evaluated using Bayesian Pearson's correlation coefficients. In the 41 PwPD included in this study, spatiotemporal gait parameters were significantly worse in free-living environments than in clinics and at lower speeds than at higher speeds. The fit of the walking speed distribution to the bimodal Gaussian model (adjustability of gait speed) in free-living environments was related to spatiotemporal gait parameters, severity of Parkinson's disease, number of falls, and quality of life. The findings suggest that gait control, which involves adjusting gait speed according to context, differs between clinics and free-living environments in PwPD. Gait assessments for PwPD in both clinical and free-living environments should interpret gait impairments in a complementary manner.

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated adult zebrafish as a model for Parkinson’s Disease

Dopamine (DA) is a catecholamine neurotransmitter that works to regulate cognitive functions. Patients affected by Parkinson’s Disease (PD) experience a loss of dopaminergic neurons and downregulated neural DA production. This leads to cognitive and physical decline that is the hallmark of PD for which no cure currently exists. Danio rerio, or zebrafish, have become an increasingly popular disease model used in PD pharmaceutical development. This model still requires extensive development to better characterize which PD features are adequately represented. Furthermore, the great majority of PD zebrafish models have been performed in embryos, which may not be relevant towards age-related human PD. As an improvement, mature D. rerio were treated with neurotoxic prodrug 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) through intraperitoneal injection to induce parkinsonism. Behavioral analysis confirmed disparities in movement between saline-injected control and the MPTP-injected experimental group, with swim distance and speed significantly lowered seven days after MPTP injection. Simultaneously, cognitive decline was apparent in MPTP-injected zebrafish, demonstrated by decreased alternation in a y-maze. RT-qPCR confirmed trends consistent with downregulation in Parkinsonian genetic markers, specifically DA transporter (DAT), MAO-B, PINK1. In summary, mature zebrafish injected with MPTP present with similar movement and cognitive decline as compared to human disease. Despite its benefits, this model does not appear to recapitulate pathophysiology of the disease with the full profile of expected gene downregulation. Because of this, it is important that researchers looking for pharmacological interventions for PD only use this zebrafish model when targeting the human-relevant PD symptoms and causes that are represented.

Functional efficacy of the MAO-B inhibitor safinamide in murine substantia nigra pars compacta dopaminergic neurons in vitro: A comparative study with tranylcypromine

Safinamide (SAF) is currently used to treat Parkinson's disease (PD) symptoms based on its theoretical ability to potentiate the dopamine (DA) signal, blocking monoamine oxidase (MAO) B. The present work aims to highlight the functional relevance of SAF as an enhancer of the DA signal, by evaluating its ability to prolong recovery from DA-mediated firing inhibition of DAergic neurons of the substantia nigra pars compacta (SNpc), compared to another MAO antagonist, tranylcypromine (TCP). Using multielectrode array (MEA) and single electrode extracellular recordings of spontaneous spikes from presumed SNpc DAergic cells in vitro, we show that SAF (30 μM) mildly prolongs the DA-mediated firing inhibition, as opposed to the profound effect of TCP (10 μM). In patch-clamp recordings, we found that SAF (30 μM) significantly reduced the number of spikes evoked by depolarizing currents in SNpc DAergic neurons, in a sulpiride (1 μM) independent manner. According to our results, SAF marginally potentiates the DA signal in SNpc DAergic neurons, while exerting an inhibitory effect on the postsynaptic excitability acting on membrane conductances. Thus, we propose that the therapeutic effects of SAF in PD patients partially depends on MAO inhibition, while other MAO-independent sites of action could be more relevant.

Exploring the Role of Reactive Oxygen Species in the Pathogenesis and Pathophysiology of Alzheimer's and Parkinson's Disease and the Efficacy of Antioxidant Treatment.

Alzheimer's (AD) and Parkinson's Disease (PD) are life-altering diseases that are characterised by progressive memory loss and motor dysfunction. The prevalence of AD and PD is predicted to continuously increase. Symptoms of AD and PD are primarily mediated by progressive neuron death and dysfunction in the hippocampus and substantia nigra. Central features that drive neurodegeneration are caspase activation, DNA fragmentation, lipid peroxidation, protein carbonylation, amyloid-β, and/or α-synuclein formation. Reactive oxygen species (ROS) increase these central features. Currently, there are limited therapeutic options targeting these mechanisms. Antioxidants reduce ROS levels by the induction of antioxidant proteins and direct neutralisation of ROS. This review aims to assess the effectiveness of antioxidants in reducing ROS and neurodegeneration. Antioxidants enhance major endogenous defences against ROS including superoxide dismutase, catalase, and glutathione. Direct neutralisation of ROS by antioxidants protects against ROS-induced cytotoxicity. The combination of Indirect and direct protective mechanisms prevents ROS-induced α-synuclein and/or amyloid-β formation. Antioxidants ameliorate ROS-mediated oxidative stress and subsequent deleterious downstream effects that promote apoptosis. As a result, downstream harmful events including neuron death, dysfunction, and protein aggregation are decreased. The protective effects of antioxidants in human models have yet to directly replicate the success seen in cell and animal models. However, the lack of diversity in antioxidants for clinical trials prevents a definitive answer if antioxidants are protective. Taken together, antioxidant treatment is a promising avenue in neurodegenerative disease therapy and subsequent clinical trials are needed to provide a definitive answer on the protective effects of antioxidants. No current treatment strategies have significant impact in treating advanced AD and PD, but new mimetics of endogenous mitochondrial antioxidant enzymes (Avasopasem Manganese, GC4419 AVA) may be a promising innovative option for decelerating neurodegenerative progress in the future at the mitochondrial level of OS.

Serotonin syndrome caused by escitalopram in Parkinson’s disease psychosis: a case report

BackgroundSerotonin syndrome and Parkinson’s disease (PD) are two diseases whose symptoms partially overlap; this poses challenges in distinguishing them in clinical practice. Early manifestations such as tremor, akathisia, diaphoresis, hypertonia and hyperreflexia are common in mild-to-moderate serotonin syndrome and can also occur in PD. Without prompt recognition and treatment, serotonin syndrome can rapidly progress, potentially leading to severe complications such as multiple organ failure within hours. Given their disparate treatment strategies, accurate clinical distinction is crucial for effective treatment. This case study explores a patient with serotonin syndrome triggered by escitalopram in the context of PD psychosis (PDP), providing insights into diagnosis and treatment planning.Case presentationA 75-year-old Asian woman with a one-year history of PD, a two-month history of PDP, and a six-year history of depression presented with symptoms including hyperreflexia, tremor, hypertonia, impaired level of consciousness, and inappropriate behavior following a recent one-month adjustment in medication. Initially suspected of being drug-induced parkinsonism or worsening PD, therapeutic drug monitoring revealed warning levels of escitalopram. Subsequent diagnoses confirmed serotonin syndrome. This syndrome may result from increased cortical serotonin activity at the serotonin2A receptor due to dopamine and serotonin imbalances in PDP, compounded by increased dopamine-mediated serotonin release. Additionally, being an intermediate metabolizer of cytochrome P450 enzyme 2C19, the patient experienced excessive escitalopram accumulation, exacerbating her condition.ConclusionsThis case underscores the critical need to differentiate between symptoms of serotonin syndrome and PD, particularly in manifestations like tremor and hypertonia. Careful consideration of receptor profiles in patients with PDP is essential when selecting antidepressants to mitigate the risk of serotonin syndrome.